Gene sheds more light on age-related blindness

US researchers have identified mutations in two genes that together account for nearly three-quarters of all cases of age-related macular degeneration (AMD), a common cause of blindness in the elderly. The study, carried out by scientists based at Columbia University Medical Center in New York, builds on work published by several groups last year - in which mutations in a key immune system gene were found to greatly increase the risk of AMD. Now, findings published in the journal Nature Genetics show that another immune system gene also plays a key role in the condition.

AMD causes the gradual degeneration of the central part of the retina, an area known as the macula, which eventually leads to a complete loss of central vision. Last year, several US teams discovered that mutations in a single gene greatly increase the likelihood that a person will develop AMD. The gene makes an immune system protein called complement factor H, and the scientists think that the mutated version leads to excessive inflammation. However, the Columbia team found that about 29 per cent of people with a factor H gene mutation had not been diagnosed with AMD, leading them to search for additional genetic risk factors.

In the latest study, the scientists decided to focus on genes that make other immune system proteins, working in the same biological 'pathway' as factor H. They looked at DNA samples from 1,300 people, and identified the factor B gene as another risk factor for AMD. It seems that 74 per cent of patients have mutations in either one or both of the factor H and factor B genes, with no protective versions of either gene. 'I am not aware of any other complex disease where nearly 75 per cent of genetic causality has been identified', said lead author Rando Allikmets.

The discovery makes good biological sense, say the researchers, since factor B activates the body's inflammation response, whereas factor H holds the same process in check. So a protective version of factor B can guard against AMD, even in people with an at-risk version of factor H - and vice versa, say the team. 'In just a few short years we've gone from knowing very little about what causes AMD to knowing quite a lot', said Dr Allikmets, adding 'we now have clear targets for early therapeutic intervention'.

However, the specific triggers that cause AMD are still unknown, and the researchers are now searching for possible bacterial and viral culprits. A spokesperson for the UK Macular Disease Society described the research as 'a very useful part of the jigsaw'. But, he told the BBC News website, 'it will take seven to ten years before we will see any cure for AMD'.